tert-butyl 4-(1-methyl-1H-pyrrole-2-carbonyl)piperidine-1-carboxylate | 1352725-11-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: tert-butyl 4-(1-methyl-1H-pyrrole-2-carbonyl)piperidine-1-carboxylate
• 英文别名: Tert-butyl 4-(1-methylpyrrole-2-carbonyl)piperidine-1-carboxylate；tert-butyl 4-(1-methylpyrrole-2-carbonyl)piperidine-1-carboxylate
• CAS: 1352725-11-1
• 化学式: C₁₆H₂₄N₂O₃
• 分子量: 292.378
• InChiKey: APADAVMDVMUKON-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  51.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(1-methyl-1H-pyrrole-2-carbonyl)piperidine-1-carboxylate 在 三乙胺 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 52.0h， 生成 (1-(5-amino-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)piperidin-4-yl)(1-methyl-1H-pyrrol-2-yl)methanone dioxalate
  参考文献：
  名称：

  Heteroaromatic and Aniline Derivatives of Piperidines As Potent Ligands for Vesicular Acetylcholine Transporter

  摘要：

  To identify suitable lipophilic compounds having high potency and selectivity for vesicular acetylcholine transporter (VAChT), a heteroaromatic ring or a phenyl group was introduced into the carbonyl-containing scaffold for VAChT ligands. Twenty new compounds with ALogD values between 0.53 and 3.2 were synthesized, and their in vitro binding affinities were assayed. Six of them (19a, 19e, 19g, 19k, and 24a-b) displayed high affinity for VAChT (K-i = 0.93-18 nM for racemates) and moderate to high selectivity for VAChT over sigma(1) and sigma(2) receptors (K-i = 44-4400-fold). These compounds have a methyl or a fluoro substitution that provides the position for incorporating PET radioisotopes C-11 or F-18. Compound (-)-[C-11]24b (K-i = 0.78 nM for VAChT, 1200-fold over sigma receptors) was successfully synthesized and evaluated in vivo in rats and nonhuman primates. The data revealed that (-)-[C-11]24b has highest binding in striatum and has favorable pharmacokinetics in the brain.

  DOI：

  10.1021/jm400664x
• 作为产物：
  描述：

  1-Boc-4-哌啶甲酸 在 正丁基锂 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 5.33h， 生成 tert-butyl 4-(1-methyl-1H-pyrrole-2-carbonyl)piperidine-1-carboxylate
  参考文献：
  名称：

  Heteroaromatic and Aniline Derivatives of Piperidines As Potent Ligands for Vesicular Acetylcholine Transporter

  摘要：

  To identify suitable lipophilic compounds having high potency and selectivity for vesicular acetylcholine transporter (VAChT), a heteroaromatic ring or a phenyl group was introduced into the carbonyl-containing scaffold for VAChT ligands. Twenty new compounds with ALogD values between 0.53 and 3.2 were synthesized, and their in vitro binding affinities were assayed. Six of them (19a, 19e, 19g, 19k, and 24a-b) displayed high affinity for VAChT (K-i = 0.93-18 nM for racemates) and moderate to high selectivity for VAChT over sigma(1) and sigma(2) receptors (K-i = 44-4400-fold). These compounds have a methyl or a fluoro substitution that provides the position for incorporating PET radioisotopes C-11 or F-18. Compound (-)-[C-11]24b (K-i = 0.78 nM for VAChT, 1200-fold over sigma receptors) was successfully synthesized and evaluated in vivo in rats and nonhuman primates. The data revealed that (-)-[C-11]24b has highest binding in striatum and has favorable pharmacokinetics in the brain.

  DOI：

  10.1021/jm400664x

文献信息

• Compounds comprising 4-benzoylpiperidine as a Sigma-1-selective ligand
  申请人：Tu Zhude

  公开号：US20110311447A1

  公开（公告）日：2011-12-22

  Bipiperidinyl compounds and salts thereof are disclosed. The compounds include high affinity ligands for σ 1 receptors. Some compounds are also highly selective for σ 1 receptor compared to σ 2 receptor. Compounds can comprise radioisotopes, including 18 F or 11 C. Radiolabeled compounds can be used as probes for imaging distribution of σ 1 receptor in a subject such as a human using positron emission tomography (PET) scanning.

  双哌啶基化合物及其盐被披露。这些化合物包括对σ1受体具有高亲和力的配体。一些化合物相对于σ2受体也具有高选择性。化合物可以包含放射性同位素，包括18F或11C。放射标记的化合物可用作探针，用于通过正电子发射断层扫描（PET扫描）在受试者（如人类）中成像σ1受体的分布。
• Ni-Catalyzed Suzuki–Miyaura Cross-Coupling of Aliphatic Amides on the Benchtop
  作者：Milauni M. Mehta、Timothy B. Boit、Jacob E. Dander、Neil K. Garg

  DOI：10.1021/acs.orglett.9b03434

  日期：2020.1.3

  Suzuki-Miyaura cross-couplings of amides offer an approach to the synthesis of ketones that avoids the use of basic or pyrophoric nucleophiles. However, these reactions require glovebox manipulations, thus limiting their practicality. We report a benchtop protocol for Suzuki-Miyaura cross-couplings of aliphatic amides that utilizes a paraffin capsule containing a Ni(0) precatalyst and NHC ligand. This

  酰胺的 Suzuki-Miyaura 交叉偶联提供了一种避免使用碱性或自燃亲核试剂的酮合成方法。然而，这些反应需要手套箱操作，从而限制了它们的实用性。我们报告了脂肪族酰胺的 Suzuki-Miyaura 交叉偶联的台式方案，该方案利用含有 Ni(0) 预催化剂和 NHC 配体的石蜡胶囊。该方法范围广泛，可扩展，并提供了一种用户友好的方法将脂肪酰胺转化为烷基芳基酮。
• Nickel-Catalyzed Suzuki–Miyaura Coupling of Aliphatic Amides
  作者：Timothy B. Boit、Nicholas A. Weires、Junyong Kim、Neil K. Garg

  DOI：10.1021/acscatal.7b03688

  日期：2018.2.2

  amide-based substrate and the boronate coupling partner and proceeds in the presence of heterocycles and epimerizable stereocenters. Moreover, a gram-scale Suzuki–Miyaura coupling/Fischer indolization sequence demonstrates the ease with which unique polyheterocyclic scaffolds can be constructed, particularly by taking advantage of the enolizable ketone functionality present in the cross-coupled product. The

  我们报告了镍催化的脂族酰胺衍生物的Suzuki-Miyaura偶联。先前的研究表明，脂族酰胺衍生物可以经历Ni催化的碳-杂原子键的形成，但是使用脂族酰胺衍生物形成Ni介导的C-C键仍然很困难。本文公开的偶联相对于基于酰胺的底物和硼酸酯偶联配偶体都容许相当大的变化，并且在存在杂环和可差向异构的立体中心的情况下进行。此外，克级的Suzuki-Miyaura偶联/ Fischer吲哚化序列证明了构建独特的多杂环支架的简便性，特别是利用了交叉偶联产物中存在的可烯化的酮官能团。
• Heteroaromatic and Aniline Derivatives of Piperidines As Potent Ligands for Vesicular Acetylcholine Transporter
  作者：Junfeng Li、Xiang Zhang、Zhanbin Zhang、Prashanth K. Padakanti、Hongjun Jin、Jinquan Cui、Aixiao Li、Dexing Zeng、Nigam P. Rath、Hubert Flores、Joel S. Perlmutter、Stanley M. Parsons、Zhude Tu

  DOI：10.1021/jm400664x

  日期：2013.8.8

  To identify suitable lipophilic compounds having high potency and selectivity for vesicular acetylcholine transporter (VAChT), a heteroaromatic ring or a phenyl group was introduced into the carbonyl-containing scaffold for VAChT ligands. Twenty new compounds with ALogD values between 0.53 and 3.2 were synthesized, and their in vitro binding affinities were assayed. Six of them (19a, 19e, 19g, 19k, and 24a-b) displayed high affinity for VAChT (K-i = 0.93-18 nM for racemates) and moderate to high selectivity for VAChT over sigma(1) and sigma(2) receptors (K-i = 44-4400-fold). These compounds have a methyl or a fluoro substitution that provides the position for incorporating PET radioisotopes C-11 or F-18. Compound (-)-[C-11]24b (K-i = 0.78 nM for VAChT, 1200-fold over sigma receptors) was successfully synthesized and evaluated in vivo in rats and nonhuman primates. The data revealed that (-)-[C-11]24b has highest binding in striatum and has favorable pharmacokinetics in the brain.